Synonym name: Methylisochondodendrine; 7,7'-O,O-Dimethylisochondodendrine
Catalogue No.: BP0433
Cas No.: 518-94-5
Formula: C₃₈H₄₂N₂O₆
Mol Weight: 622.762
Botanical Source: Alkaloid from Chondodendron tomentosum, Cissampelos insularis, Cissampelos pareira, Cleistopholis staudtii, Cyclea tonkinensis, Epinetrum cordifolium, (preferred genus name Albertisia), Epinetrum mangenotii, Epinetrum villosum, Heracleum wallichi, Limaci

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HPLC of Cycleanine

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Cycleanine (CAS No.: 518-94-5) is an alkaloid compound derived from natural plants, attracting attention for its remarkable antagonistic activity of vascular selective calcium channels. As a highly effective Ca²⁺ antagonist, rotulatamine not only shows good pharmacological activity in cardiovascular diseases but has also been widely studied for its pain relief, muscle relaxation, and anti-inflammatory effects. Furthermore, recent studies have shown that cyclocycline shows potential in tumor treatment, especially in the antitumor activity of ovarian cancer, by regulating cell apoptosis pathways. Lung cancer, as a malignant tumor with one of the highest incidence and mortality rates worldwide, has been revealed by research revealing that rotamine may mediate anti-cancer effects through multiple molecular targets, expanding its clinical application possibilities.

This paper aims to systematically review the chemical structure and physicochemical properties of Rhicantin, plant origin and extraction methods, pharmacological activity, and mechanism of action, focusing on its molecular targets and pathways of action in tumor treatment, evaluating its druggability and pharmacokinetic characteristics, and looking ahead to its future clinical application prospects, providing theoretical basis and research directions for natural product pharmacology and new drug development.

Chemical structure and physicochemical properties

Runhuan Tengkaloid is a complex alkaloid compound with the molecular formula C₃₆H₄₀N₂O₈ and a molecular weight of 634.78. Its structural features include multiple circular frameworks containing multiple oxidized functional groups and nitrogen atoms, giving it unique chemical properties and biological activity. The LogP value of rotula ornaline is 4.57, indicating high lipid solubility, which facilitates penetration of cell membranes, but may also affect its water solubility and bioavailability. Its topological pole surface area (TPSA) is 69.17 Ų, indicating moderate polarity that may affect its binding ability to biomacromolecules and their distribution in vivo.

Rotula vine contains six hydrogen bond receptors, which are important for its binding to protein targets. Although there is currently no clear data on its blood-brain barrier penetration, hepatotoxicity, cardiotoxicity, or hERG channel inhibition, its structural characteristics suggest that further systematic evaluation of its safety and pharmacokinetic properties is needed.

Plant Origins and Extraction Methods

Cycla spp. is mainly found in plants of the Cycla family, especially in the rhizomes and leaves of plants of the genus Cyclea (Cyclea spp.). In traditional Chinese medicine, the Ringed Vine plant is used as a medicinal material for promoting blood circulation, removing blood stasis, relieving pain, and anti-inflammatory effects. Modern extraction techniques mostly use organic solvent extraction combined with column chromatography separation and purification to obtain high-purity Rhizolin alkaloids.

Common extraction processes include:

1. Crude extraction: Use ethanol or methanol to extract dried plant material by reflux, with extraction time generally ranging from several hours to one day and night.
2. Separation and purification: Separation of runtiline is achieved through liquid-liquid partitioning, silica gel column chromatography, or reversed-phase high-performance liquid chromatography (RP-HPLC).
3. Identification and purity testing: Mass spectrometry (MS), nuclear magnetic resonance (NMR), and infrared spectroscopy (IR) are used to confirm structure and purity.

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved the extraction efficiency and purity of Runhuan Tengji, laying the foundation for its industrial production.

Pharmacological activity research

Antagonism of vascular selective calcium channels

As a highly effective vascular-selective Ca²⁺ antagonist, cyclocycline can block voltage-dependent calcium channels, inhibit calcium ion influx, thereby relaxing vascular smooth muscle, reducing vascular resistance, lowering blood pressure, and improving microcirculation. Both in vitro and in vivo experiments confirmed its significant inhibitory effect on vascular smooth muscle cells, with minimal effect on cardiomyocytes, demonstrating good selectivity.

Relieves pain and relaxes muscles

Cyclocycline regulates nerve conduction and muscle excitability, showing significant analgesic and muscle relaxation effects. Animal model studies have shown that rotamine can alleviate inflammatory and neuropathic pain, and its muscle-relaxing effect helps alleviate symptoms of spastic diseases.

Anti-inflammatory effects

Rotula rotamine exhibits anti-inflammatory activity by inhibiting the release of inflammatory mediators and activating inflammatory signaling pathways. It can downregulate the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, reducing inflammatory responses and demonstrating potential value in treating inflammatory diseases.

Antitumor activity

In recent years, research on ringocycline in tumor treatment has gradually increased, especially showing significant anti-cancer potential in ovarian and lung cancer models. It demonstrates multi-target, multi-mechanism anti-tumor activity by inducing tumor cell apoptosis and inhibiting cell proliferation and migration. Related studies suggest that Runhuan Tengsine can exert its effects by regulating various signaling pathways and molecular targets.

Mechanism of action and molecular targets

The mechanism of action of runtiline involves multiple signaling pathways and key molecular targets, with its regulatory role in tumor cells receiving particular attention.

Calcium channel blocking mechanism

Cyclocycline blocks Ca²⁺ influx by binding to voltage-dependent L-type calcium channels, lowering intracellular calcium concentration, causing vascular smooth muscle relaxation, and relieving vascular spasms and hypertension.

Anti-tumor-related molecular targets

In lung cancer and other tumor models, the key targets of rotamine action include:

• BCL2: As an anti-apoptotic protein, downregulation of BCL2 promotes tumor cell apoptosis.
• STAT3: Signal transduction and transcription activator factor 3, regulates cell proliferation and immune escape; rotuline inhibits its activity and blocks tumor growth signals.
• ESR2 (estrogen receptor β): Regulates cell proliferation and apoptosis; ringine may influence tumor cell fate by modulating ESR2 expression.
• MAPT (microtubule-associated protein Tau): Involved in cytoskeletal stabilization, affecting cell migration and division.
• PIK3CG :P I3Kγ subtype, regulates the PI3K/Akt signaling pathway; rotula inhibits its activity and blocks cell survival signals.
• RELA (NF-κB p65 subunit): a key transcription factor that regulates inflammation and cell survival. Rota inhibits NF-κB signaling and promotes apoptosis.
• MAPK1/MAPK8: Mitogen-activated protein kinase, involved in cell proliferation and stress responses; rotula vine regulates its activity and influences cell fate.
• CASP9: Caspase 9, initiates the endogenous apoptosis pathway; rotolocycline activates CASP9, inducing programmed cell death.
• PPARG: Peroxisome proliferators activate receptor γ, regulate metabolism and cell differentiation, and rhicycline may mediate anti-tumor effects by modulating PPARG.

Activation of the apoptosis pathway

Ringo-ringed ketalin activates mitochondria-dependent apoptosis pathways, inducing cytochrome C release, activating CASP9 and downstream effectases, ultimately leading to tumor cell apoptosis. Additionally, its anti-inflammatory and antioxidant effects help regulate the tumor microenvironment and inhibit tumor progression.

Druggability evaluation and pharmacokinetics

The drug-worthiness evaluation of Rhitodenine is currently in its early stages. Its large molecular weight (634.78 Da) and high lipophilubility (LogP=4.57) suggest that oral bioavailability may be limited, but its moderate polar surface area (TPSA=69.17 Ų) favors membrane penetration. The number of hydrogen bond receptors is 6, meeting the basic requirements for drug molecule binding to the target.

Currently, there is a lack of systematic experimental data on blood-brain barrier penetration, hepatotoxicity, cardiotoxicity, and hERG channel inhibition, and further safety evaluation is needed in the future. Pharmacokinetics, the absorption, distribution, metabolism, and excretion characteristics of rotula rotamine remain unclear, and further studies on its half-life, bioavailability, and metabolic pathways through in vivo and in vitro models are needed.

Based on its structural characteristics, the drug design of rotula canine can improve water solubility and pharmacokinetic performance through structural modification, thereby increasing its clinical application potential.

Prospects and outlooks for clinical applications

As a natural product, Rhinosine has multiple pharmacological activities and potential clinical applications. Its vascular selective calcium antagonism in cardiovascular diseases offers a new therapeutic approach for hypertension and vascular spasm-related conditions. Its pain relief and muscle relaxation effects give it potential applications in neuromuscular diseases.

More importantly, the multi-target mechanism of rulina in cancer treatment, especially its anti-tumor activity in ovarian and lung cancers, provides new directions for the development of natural product anticancer drugs. Future research should focus on in-depth analysis of its anti-tumor mechanisms, optimizing dosage forms and administration regimens, and conducting preclinical safety and efficacy evaluations.

In addition, by integrating modern drug design technologies, such as computer-aided drug design (CADD) and nanocarrier delivery systems, the efficacy and bioavailability of rotamine are expected to be enhanced, promoting its clinical application.

Conclusion

As a natural alkaloid with multiple biological activities, Rhinoquin shows broad application prospects in cardiovascular diseases, pain management, and tumor treatment. Its unique chemical structure endows it with highly efficient vascular-selective calcium channel blocking capabilities and multi-target anti-tumor effects, showing significant potential especially in regulating apoptosis pathways.

Although its druggability and pharmacokinetic characteristics are not yet fully understood, with advances in extraction and purification technology and molecular biology research, alkaloid is expected to become an important candidate molecule in the fields of natural product pharmacology and anticancer drug development. Future research should focus on safety evaluation, deepening mechanisms of action, and preclinical studies to promote the clinical translation of rotamine and provide new strategies and drug options for the treatment of related diseases.